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NCT Number: NCT02915861

Eschar Investigations in Scrub Typhus

This is an observational study of patients with scrub typhus (rapid diagnostic test/quantitative polymerase chain reaction (RDT/qPCR) positive) and an inoculation eschar present on examination, recruited from Chiangrai Prachanukroh Hospital, North of Thailand.

In this study, we aim to:

* Investigate relevant pathogen dissemination dynamics, early innate immune response, and pathogen-host interactions in scrub typhus using a minimal set of easily accessible samples; the inoculation eschar (crust or biopsy), whole blood and - where possible - a lymph node fine-needle aspiration (FNA). * Determine the potential use of the inoculation eschar for improving early diagnostics and assessing the diversity of human pathogenic strains; by evaluating non-invasive swabs and scrapings, as well as biopsies for molecular diagnostics templates. * Dissect the underlying patho-biology associated with the inoculation eschar and in a subgroup, including the draining lymph node; by defining the spectrum of infected cells via microscopy and double-immune labeling; by determining cytokine and RNA gene expression profiles in blood peripheral blood mononuclear cell (PBMCs) and eschar samples.

Data sharing:

No future analysis or study of legacy data/specimens including data sharing for purposes not specified in the protocol will be done without seeking further regulatory (EC/IRB) approval

* Any requests for data sharing will be considered by MORU's data sharing committee * Any data subsequently shared will be anonymised and will not include personal identifiers

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Key information

Conditions

Scrub Typhus Bacterial Infections Bacterial Infections and Mycoses Gram-Negative Bacterial Infections Infections Rickettsiaceae Infections Vector Borne Diseases

Age range

7 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Chiangrai Prachanukroh Hospital

Chiang Rai, Thailand

About this study

Scrub typhus patients will be recruited into the scrub typhus patient (EXP) arm of the study. There will be 3 sub-groups:

  • EXPa (n=12) will have blood and non-invasive eschar samples collected (consent to study, declined biopsy).
  • EXPb (n=12) will have blood, non-invasive eschar samples, and an eschar biopsy collected (consent to study, draining lymph node (LN) inaccessible).
  • EXPc (n=12) will have blood, non-invasive eschar samples, eschar biopsy, and LN FNA collected (consent to study, draining LN accessible).

Samples will be collected at baseline (all) and 2 weeks (blood only).

Control participants will be recruited into the scrub typhus control.

  • EXC (n=12) are healthy individuals, attending hospital for elective/minor surgery or treatment of minor skin injury, and normally reside in a scrub typhus endemic region. Blood and a skin sample will be collected at baseline only.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Scrub Typhus Patients (EXP) inclusion criteria:

  • Age ≥7 years old.
  • Presentation to hospital with fever in ≤14 days and a clinical suspicion of typhus.
  • Eschar observed on examination.
  • Scrub typhus RDT positive or OT qPCR positive (if qPCR available at local site by time of study initiation).
  • Willingness to participate in the study. Written informed consent obtained from the patient (≥18 years old) or, written informed assent from participant (≥7 to <18years old) along with written informed consent from participant's parent(s)/legal guardian(s).

Scrub Typhus Controls (EXC) inclusion criteria:

  • Age ≥7 years old.
  • Clinically well, attending elective/minor surgery or for treatment of minor skin injury.
  • Historical diagnosis of scrub typhus (RDT, serology, and/or PCR positivity) more than 2 years ago or living in an endemic area with high risk of previous exposure.
  • Willingness to participate in the study. Written informed consent obtained from the patient (≥18 years old) or written informed assent from participant (≥7 to <18years old) along with written informed consent from participant's parent(s)/legal guardian(s).

Scrub Typhus Patients (EXP) exclusion criteria:

  • Current TB or TB treatment in ≤6 months (contains OT-effective antimicrobials)
  • Documented HIV infection, use of steroids, chemotherapy, other immunosuppressants, or herbal remedies containing steroids, and/or pregnancy

Scrub Typhus Controls (EXC) exclusion criteria:

  • Significant acute intercurrent illness at the time of admission including fever >37.5˚C or infection (including TB) requiring antibiotics
  • Documented HIV infection, use of steroids, chemotherapy, other immunosuppressants, or herbal remedies containing steroids, and/or pregnancy

Treatment and study plan

Non-invasive eschar samples + blood

Other

EXPa (n=12) will have blood and non-invasive eschar samples collected (consent to study, declined biopsy).

Non-invasive eschar samples+eschar biopsy+blood

Other

EXPb (n=12) will have blood, non-invasive eschar samples, and an eschar biopsy collected (consent to study, draining LN inaccessible).

Non-invasive eschar samples+eschar biopsy+lymph node fine-needle aspiration biopsy+blood

Other

EXPc (n=12) will have blood, non-invasive eschar samples, eschar biopsy, and LN FNA collected (consent to study, draining LN accessible).

Blood+Skin sample

Other

Controls (EXC, n=12) are healthy individuals, attending hospital for elective/minor surgery or treatment of minor skin injury, and normally reside in a scrub typhus endemic region. Blood and a skin sample will be collected at baseline only.

Primary outcomes

  1. Phenotypic characterisation of the major subset of Orientia tsutsugamushi (OT) infected leucocytes within eschar, lymph node, and blood during the dissemination phase of OT in vivo.

    Time frame: 2 years

  2. Characterisation of cytokine and RNA gene expression profiles within the eschar, lymph node, and blood in vivo and comparisons with profiles of uninfected target cells.

    Time frame: 2 years

Secondary outcomes

  1. Establishing the usefulness of non-invasive eschar samples from patients with acute scrub typhus for diagnostics for OT and for genotyping +/- whole-genome sequencing.

    Time frame: 2 years

  2. Define and contrast the eschar histo-pathological findings in this study in Thailand to previous findings from Laos, where the Gilliam strain predominates.

    Time frame: 2 years

  3. Comparisons to parallel studies in the non-human primate model with emphasis on dissemination dynamics, immunomodulation, and the innate and adaptive immune responses to OT; contributing to vaccine development.

    Time frame: 2 years

Sponsors and collaborators

Lead sponsor

University of Oxford

Other

Collaborators

  • Chiangrai Prachanukroh Hospital

Registry information

Official study title

Eschar Investigations to Improve Diagnostics, Understand Early Immune Responses and Characterize Strains for Vaccines in Scrub Typhus

Acronym: EXIST

Important dates

Study start
2017
Primary completion
2021
Study completion
2021
First posted
Sep 27, 2016
Registry last updated
Aug 5, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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